Dissolution testing involves physical evaluation of solid dosage forms such as capsules and tablets. Results of dissolution testing are useful in studying drug release characteristics of the dosage form and evaluating equipment and processes used in forming individual doses. To ensure uniformity in testing, entities such as the United States Pharmacopeia (USP) and the European Pharmacopeia provide guidelines for equipment used in dissolution testing.
Under these guidelines, typically a capsule or tablet is deposited in a test vessel containing dissolution media intended to emulate, for example, stomach or intestinal fluids. The vessel is maintained at a constant temperature, and the vessel contents are agitated at a specified speed. Samples of the resulting solution are then taken at predetermined times and analyzed using techniques such as high performance liquid chromatography (HPLC) and spectral analysis.
Conventional dissolution testing systems include pumps and tubing for transferring the samples from the test vessels to the analytical equipment. The samples transferred using such an arrangement may be as large as 10 ml. One disadvantage of using such large-volume samples is that the samples may contain undissolved particles that dissolve during the transfer process (termed secondary dissolution), resulting in inaccurate values for the dissolution rate. Another disadvantage of large-volume samples is that the vessel hydrodynamics are disrupted for the entire time the sample is being withdrawn from the vessel. For example, a typical transfer rate is 10 ml per minute, resulting in a full minute of disruption of the vessel hydrodynamics to withdraw a single 10-ml sample. In addition, withdrawing multiple large samples necessitates replenishing the sample media in the test vessel to maintain adequate volume for proper agitation of the mixture, adding complexity to the process.
Disadvantages of using tubing to transfer the samples include the inconvenience of purging the tubing after each sample is transferred and the risk of carryover (i.e., contamination) if purging is incomplete. Components of the sample may also adsorb to the inner surface of the tubing, producing an inaccurate dissolution rate.
Another disadvantage of prior art instruments is their inability to handle all possible dosage forms within a single test run or to handle the different dosage forms without modifying the instrument for each different dosage form. For example, some dosage forms, particularly capsules, float when placed into a fluid. These dosage forms must be inserted into “sinkers” that provide the needed additional weight to submerge the dosage form in the dissolution media. Alternatively, the dosage form may be inserted into a basket that is submerged in the dissolution media. Sinkers and tablets that sink can be placed directly into a dissolution vessel and agitated using a mixing paddle. The baskets themselves can be rotated or otherwise agitated, eliminating the need for a mixing paddle. Typically prior art systems are not able to handle tablets (and other dosage forms that are dispensed directly into the dissolution media) along with sinkers and baskets all within a single run. The dosage forms typically must be grouped by type and the instrument set up for that specific type of dosage form, often requiring modification of the system.
Therefore, it would be desirable to provide a dissolution testing system that overcomes the aforementioned and other disadvantages.